Wnt-mediated self-renewal of neural stem/progenitor cells.
In this work we have uncovered a role for Wnt signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells in the subventricular zone of the developing E14.5 mouse brain. Responding cell populations were enriched for self-renewing stem cells in primary culture, suggesting that Wnt signaling is a hallmark of self-renewing activity in vivo. We also tested whether Wnt signals directly influence neural stem cells. Using inhibitors of the Wnt pathway, we found that Wnt signaling is required for the efficient cloning and expansion of single-cell derived populations that are able to generate new stem cells as well as neurons, astrocytes, and oligodendrocytes. The addition of exogenous Wnt3a protein enhances clonal outgrowth, demonstrating not only a critical role for the Wnt pathway for the regulation of neurogenesis but also its use for the expansion of neural stem cells in cell culture and in tissue engineering.
Kalani
M Yashar S
MY
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cheshier
Samuel H
SH
Cord
Branden J
BJ
Bababeygy
Simon R
SR
Vogel
Hannes
H
Weissman
Irving L
IL
Palmer
Theo D
TD
Nusse
Roel
R
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D060466:Axin Protein; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D060466:Axin Protein; C111729:Axin2 protein, mouse; D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse